The broad objectives of this project concern the development of new approaches to the biochemistry an physiology of human platelets and subcellular platelet organelles, particularly asthey relate to thrombosis and disorders of hemostasis and coagulation. The research will also represent an extension of cncepts and techniques deveoped in this laboratory over the past fifteen years. Procedures will be devised for the further subfractionation of platelet granules and membranes into 'individual populations' in order to permit more precise characterization of their ultrastructual and biochemical propertis. These refinements wll be implemented for the purpose of studying platlet organells from patients with disordersof platelet function. Another major aspect of ourresearch will be devoted to a studyof platelet gangliosides, globosides, proteins and proteolipids. These platelet components wll receive special attention aspossible receptor substaces for serotnin, nucleoides and certain drugs. It is anticipated that newly deveoped affinity chromatography methods wll constitute one of our main approaces to researc on platelet receptos. Concomiantly we wll be continuing to investigate an original approach to the dynamics of human platelet, platelet lipid and platelet sub--namely, nuclear magnetic resonancespectrospectroscpy (NMR). Our preliminary investigations indicate that NMR will furnish new information concerning complex formation between platelets, platelet membranes and 'effector' compounds. It sould also bepossible to identify the cemical groups involved in such interactions. Inhibition of the activity of these chemical groups by structural analogues may lead to the development of drug therapy fo the prevention of thrombosis. Thus our ultimate goal continues to be the more precise definition of the unique contribution of platelets and platelet organelles to the hemostatic process as well as to occlusive vascular disease.